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Pathway Description
Difelikefalin Opioid Agonist Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-08-24
Last Updated: 2023-11-27
Difelikefalin is a kappa opioid receptor agonist used in the treatment of moderate-to-severe pruritus (itchy skin) associated with chronic kidney disease in patients undergoing hemodialysis. It is administered via intravenous injection at the end of each hemodialysis treatment. Kappa receptors have been associated with itching sensation since 1984.
In the spinal cord, Difelikefalin binds to the kappa-type opioid receptor. The Kappa-opioid receptor is coupled with G-protein receptors. Difelikefalin stimulates the exchange of GTP for GDP on the G-protein complex. The G-protein system inhibits adenylate cyclase which prevents ATP from being synthesized into cAMP which causes a decrease in intracellular cAMP. The activated G-proteins also close N-type voltage-operated calcium channels which prevents calcium from entering the neuron, and it opens calcium-dependent inwardly rectifying potassium channels which causes sodium to leave the neuron. This results in hyperpolarization and reduced neuronal excitability. This causes a neuroinhibitory effect of the itching sensation at the spinal cord level.
References
Difelikefalin Opioid Agonist Pathway References
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https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214916s000lbl.pdf
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Pubmed: 16710414
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